ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Hydrophobic and Hydrophilic Interactions  (2)
  • Nature Publishing Group (NPG)  (2)
  • American Physical Society (APS)
  • 1
    facet.materialart.
    Unknown
    SCF(FBXL3) ubiquitin ligase targets cryptochromes at their cofactor pocket (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-03-19
    Description: The cryptochrome (CRY) flavoproteins act as blue-light receptors in plants and insects, but perform light-independent functions at the core of the mammalian circadian clock. To drive clock oscillations, mammalian CRYs associate with the Period proteins (PERs) and together inhibit the transcription of their own genes. The SCF(FBXL3) ubiquitin ligase complex controls this negative feedback loop by promoting CRY ubiquitination and degradation. However, the molecular mechanisms of their interactions and the functional role of flavin adenine dinucleotide (FAD) binding in CRYs remain poorly understood. Here we report crystal structures of mammalian CRY2 in its apo, FAD-bound and FBXL3-SKP1-complexed forms. Distinct from other cryptochromes of known structures, mammalian CRY2 binds FAD dynamically with an open cofactor pocket. Notably, the F-box protein FBXL3 captures CRY2 by simultaneously occupying its FAD-binding pocket with a conserved carboxy-terminal tail and burying its PER-binding interface. This novel F-box-protein-substrate bipartite interaction is susceptible to disruption by both FAD and PERs, suggesting a new avenue for pharmacological targeting of the complex and a multifaceted regulatory mechanism of CRY ubiquitination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618506/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618506/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xing, Weiman -- Busino, Luca -- Hinds, Thomas R -- Marionni, Samuel T -- Saifee, Nabiha H -- Bush, Matthew F -- Pagano, Michele -- Zheng, Ning -- 5T32-HL007151/HL/NHLBI NIH HHS/ -- K99 CA166181/CA/NCI NIH HHS/ -- R01 GM057587/GM/NIGMS NIH HHS/ -- R01-CA107134/CA/NCI NIH HHS/ -- R01-GM057587/GM/NIGMS NIH HHS/ -- R21-CA161108/CA/NCI NIH HHS/ -- R37 CA076584/CA/NCI NIH HHS/ -- R37-CA-076584/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Apr 4;496(7443):64-8. doi: 10.1038/nature11964. Epub 2013 Mar 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23503662" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoproteins/chemistry/metabolism ; Binding Sites ; Cryptochromes/chemistry/*metabolism ; Crystallography, X-Ray ; Deoxyribodipyrimidine Photo-Lyase/chemistry ; Drosophila melanogaster/chemistry ; F-Box Proteins/chemistry/*metabolism ; Flavin-Adenine Dinucleotide/metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Mice ; Models, Molecular ; Protein Structure, Tertiary ; S-Phase Kinase-Associated Proteins/chemistry/metabolism ; SKP Cullin F-Box Protein Ligases/chemistry/*metabolism ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    The crystal structure of a voltage-gated sodium channel (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-07-12
    Description: Voltage-gated sodium (Na(V)) channels initiate electrical signalling in excitable cells and are the molecular targets for drugs and disease mutations, but the structural basis for their voltage-dependent activation, ion selectivity and drug block is unknown. Here we report the crystal structure of a voltage-gated Na(+) channel from Arcobacter butzleri (NavAb) captured in a closed-pore conformation with four activated voltage sensors at 2.7 A resolution. The arginine gating charges make multiple hydrophilic interactions within the voltage sensor, including unanticipated hydrogen bonds to the protein backbone. Comparisons to previous open-pore potassium channel structures indicate that the voltage-sensor domains and the S4-S5 linkers dilate the central pore by pivoting together around a hinge at the base of the pore module. The NavAb selectivity filter is short, approximately 4.6 A wide, and water filled, with four acidic side chains surrounding the narrowest part of the ion conduction pathway. This unique structure presents a high-field-strength anionic coordination site, which confers Na(+) selectivity through partial dehydration via direct interaction with glutamate side chains. Fenestrations in the sides of the pore module are unexpectedly penetrated by fatty acyl chains that extend into the central cavity, and these portals are large enough for the entry of small, hydrophobic pore-blocking drugs. This structure provides the template for understanding electrical signalling in excitable cells and the actions of drugs used for pain, epilepsy and cardiac arrhythmia at the atomic level.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266868/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266868/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Payandeh, Jian -- Scheuer, Todd -- Zheng, Ning -- Catterall, William A -- R01 NS015751/NS/NINDS NIH HHS/ -- R01 NS015751-24/NS/NINDS NIH HHS/ -- R01 NS15751/NS/NINDS NIH HHS/ -- U01 NS058039/NS/NINDS NIH HHS/ -- U01 NS058039-03/NS/NINDS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Jul 10;475(7356):353-8. doi: 10.1038/nature10238.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21743477" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arcobacter/*chemistry ; Bacterial Proteins/*chemistry/*metabolism ; Binding Sites ; Calcium/metabolism ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Hydrophobic and Hydrophilic Interactions ; *Ion Channel Gating ; Ion Transport ; Models, Molecular ; Potassium/metabolism ; Potassium Channels/chemistry/metabolism ; Protein Conformation ; Sodium/metabolism ; Sodium Channel Blockers/chemistry/metabolism/pharmacology ; Sodium Channels/*chemistry/*metabolism ; Structure-Activity Relationship ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...